This is a revised proposal for the project, Promoting Antiviral Medication Adherence in HIV Clinics, which will test the effectiveness of an intervention to promote medication adherence and improve clinical outcome for patients about to initiate combination anti-retroviral therapy. The study will be conducted in three large adult HIV outpatient clinics, treating predominantly ethnic minority men and women n Medicaid, at two major teaching hospitals in New York City (Columbia-Presbyterian and New York Hospital/Cornell University Medical Centers). "Combination therapy," with at least two anti-retroviral drugs, and usually including a protease inhibitor, has become the standard of care and is demonstrably effective in reducing HIV viral load for many patients. However, these exciting therapeutic advances bring with them major challenges with respect to medication adherence. Since patients can develop resistance and cross- resistance (to all other protease inhibitors) after only a week of missed medication, irregular use, or incomplete doses, there are serious consequences for the individual and potential public health consequences as well, since resistant viral strains can be transmitted to others. All patients in these clinics who have agreed with their doctor's recommendation to start (or switch to) combination therapy that includes a protease inhibitor will be eligible. Participants will be randomized to either the intervention of control ("usual care") arm of the study, and all will have assessments at baseline and Weeks 4, 12, and 26. The cognitive-behavioral intervention is structured and theory-driven. Delivered by a nurse educator, it focuses on maximizing accurate understanding of the medical and practical aspects of combination treatment an resolving practical barriers to adherence, maximizing belief in person control or self-efficacy, and maximizing perceived and practical social support. There will be four acute phase sessions during the first month of initiating combination therapy ("hit hard, hit early") and four maintenance sessions at successive monthly intervals. Major outcome measures include behavioral adherence and clinical effect in terms of decline in HIV RNA viral load. The primary goal of the study is to test the effectiveness of our intervention; secondary goals are to examine the relationship between adherence and clinical outcome and to identify psychiatric, psychosocial, medical, and situational predictors of adherence and clinical outcome.